J. Org. Chem. 1995,60,2938-2941
2938
Reductive and Nonreductive Aromatization of Quinol Ketal Glycals. Models for the Preparation of C-Aryl Glycoside Natural Products Kathlyn A. Parker,*,' Craig A. Coburq2 and Yung-hyo Koh Department of Chemistry, B r o w n University, Providence, Rhode Island 0 2 9 1 2
conversion of quinol ketal 2 to C-aryl glycal 3.6 Furthermore, we describe a new and potentially useful transformation, the nonreductive aromatization of the quinol ketal substrates, a process which takes place with concomitant 1,a-migration of the glycal substituent (see below). In our early studies with Lewis acidic hydride reagents, we found that borane-dimethyl sulfide (BMS)effects the reductive aromatization of quinol ketals (5 6, Table 1). Excellent yields were obtained when the reaction was allowed to proceed at room temperature.
-
Received November 21, 1994
"he gilvocarcin class of antitumor antibiotics3 (e.g. ravidomycin, l I 4 has provided inspiration for the development of novel methods for establishing the C-aryl glycoside c~nnection.~ Key steps in our own approach to the synthesis of ravidomycin are the reductive aromatization of a glycal-substituted quinol ketal (e.g. 2 3) and the concurrent or subsequent hydroboration of the enol ether double bond (i.e. 3 4h6,'
-
-
entry 1 2 3 4 5
OH OMe
MezN
a
1 ravldomycin (or enantio ravidomycin)
OMe
2
OMe hydroboration, oxidation
zation
OTBS
Table 1. Reductive Aromatization of Quinol Ketals'
substrate 5 5a Sb 5c
X
Y
H H H H OCH3
H H H Br OCH3
5d Se 1.22 moles BMSImol of substrate.
R CH3 n-Bu Ph CH3 CH3
yield(%)of6 96 88 83 85 82
However, treatment of the model substrate 7 under similar conditions (1.3 mol of BMS, room temperature), but for 14 h and with an oxidative workup, afforded not only the C-aryl glycal8 and its hydroboration product 9 but a phenolic byproduct 10 (ratio approx. 3:2:1, Table 2, entry 3). Table 2. Product Distribution as a Function of Amount of Borane OMe
OMe
8
9
'"'OR2
CH3"'
3
OTBS 48 R1 = H, R2 = TBS 4b R1 = TBS, R2 H
We have examined the potential of several hydride reducing agents for effecting the reductive aromatization of quinol ketals, particularly glycal-substituted quinol ketals. In this paper, we report the details of those studies which have resulted in optimization of the (1) Recipient of an NSF Career Advancement Award, 1992-1993. (2)Recipient of the 1991-1992 Division of Organic Chemistry
(American Chemical Society) Graduate Fellowship Award sponsored by The Rohm and Haas Co. (3) For a comprehensive survey of the literature on the gilvocarcins and reports of the first syntheses of members of this class, see (a) Matsumoto, T.; Hosoya, T.; Suzuki, K. J. Am. Chem. SOC. 1992, 114, 3568. (b) Hosoya, T.; Takashiro, E.; Matsumoto, T.; Suzuki, K. J.Am. Chem. SOC.1994,116, 1004. (4) Findlay, J.; Liu, J.-S.; Radics, L.; Rakhit, S. Can. J. Chem. 1981, 59, 3018. Rakhit, S.; Eng, C.; Baker, H.; Singh, K. J. Antibiot. 1983, 36,1490. Narita, T.; Matsumoto, M.; Mogi, IC;Kukita, K.-I.; Kawahara, R.; Nakashima, T. J.Antibiot. 1989, 42, 347. ( 5 ) For recent reviews on this subject, see (a) Suzuki, IC;Matsumoto, T. in Recent Progress in the Chemical Synthesis of Antibiotics and Related Microbial Products; Lukacs, G., Ed.; Springer: Berlin, 1993; Vol2, pp 353-403. (b) Jaramillo, C.; Knapp, S. Synthesis 1994, 1-20. (6) A preliminary report of some of the results described herein has appeared: Parker, K. A.; Coburn, C. A. J. Am Chem. SOC.1991,113, 8516. (7) For related work on reductive aromatization of quinols, see Parker, K. A,; Coburn, C. A. J. Org. Chem. 1991,56, 1666.
7
entry 1 2 3 4 5 6
10
molarratioBMSl7
8
9
10
213 313 4/3 513 613 713
52 52 47 26
0
39 24 17 11
0 0
24 36 47 45
50
0 0
lowRf 0 0 0 0 28 32
Our immediate concern was to improve the yield of glycal8 and/or hydroxypyran 9 so that we could proceed with confidence to the hydroboration of the more elaborate substrate, quinol ketal 2. The studies of Fleming and Bolke$ had indicated that the reductive cleavage of ketals by diborane is third order in borane and that each of the three hydrogens of borane is available for participation in the reduction. Therefore we chose to test the influence of borane concentration on the distribution of products derived from model compound 7. (8) (a)Bolker, H. I.; Fleming, B. I. Can J. Chem. 1975,53,2818.(b) Fleming, B. I.; Bolker, H. I. Can. J. Chem. 1974, 52, 888.
0022-3263/95/1960-2938$09.00/00 1995 American Chemical Society
J . Org. Chem., Vol. 60, No. 9, 1995 2939
Notes We carried out a series of reactions in which the amount of substrate, the solvent, the time and temperature were constant. Only the amount of boranedimethyl sulfide was varied. The results are detailed in the Experimental Section and summarized in Table 2. As expected, with increasing amounts of boranemethyl sulfide, the yield of the hydroboration product 9 increased at the expense of the reductively aromatized product 8. A decrease in the yield of the rearrangement product 10 with increasing amounts of the borane reagent was also evident. The latter effect is consistent with a mechanism in which reductive aromatization and rearrangement arise from an intermediate such as A (Scheme 1). This carbonium ion partitions to 11 (which then dehydrates to 8 ) and to B which loses a proton to afford 10. The former transformation (Ato 8 ) involves hydride trapping by the external borane species. However, in the latter transformation (A to lo), no hydride is required.
Scheme 1 Lewis acid
fi
'OH
'-(Of
oooH 111'
?Me
H OMe
BH3
8
11
A
1
-H20c
/
~
OMe
In the product mixtures from experiments in which the molar ratio of borane to substrate was at least 2:l (Table 2), a significant amount of material was found in a low Rf chromatography fraction (last column). One component of this fraction was isolated and identified as tetrahydropyran 12, presumably the result of overreduction of enol ether 8. The reduction of enol ethers to ethers by excess boranegis the subject of further study in our labs. OMe
Table 3. Product Distribution as a Function of Hydride Reagent
7
8
11
13
yield of product 11 10 0 100 0 0 5 8 0 0 0 0 0 100 0 0 100
T, "C
hydride reagent 4/3 eq BHzBrSMe2 4/3 eq 9-BBN 4/3 eq (BH30TFA-) Na+ 5 eq Red-Al 5 eq DIBAL-H 5 eq DIBAL-H 5 eq DIBAL-Ha a
10
8 0
20
20 20 20 20
-78 -78
80 25
0 75
20 0
13 0
0 1911 0 0 0 0
Inverse addition.
The inverse addition DIBAL-H procedure afforded only ether 11, the product of simple ketal reduction, and substituted anisole 8 , the product of ketal reduction and dehydration. This procedure was therefore applied in the glycal series. When glycal substituted quinol ketal 2 was added to a methylene chloride solution of DIBAL-H at -78 "C, a mixture consisting only of 3 and 14 (approximately 2:l by NMR integration) was isolated. Attempts to complete the dehydration required for efficient conversion of ketal 2 to C-aryl glycal 3 were rewarded when it was found that treatment of the mixture with phosphorus oxychloride in pyridine led, exclusively, to the recovery of the key intermediate 3. Then hydroboration followed by oxidation with basic peroxide, a procedure which has been used previously with C-aryl glycals, completed the desired sequence to afford C-aryl glycoside 4b.12
2
-+ Dibal, -780 3 inverse addition
C
H
3
g
H
%3 PY
TBSO
.
2 BH 4b H202B
NaOH
~TBS 14
12
Because the product mixture from the borane-induced reductive aromatization could be complex and because the workup was inconvenient on a large scale, we examined alternative reagents for their ability to effect the desired transformation. Product distributions which resulted from the treatment of substrate 7 with a variety of hydride-donating reagents are shown in Table 3. Procedures for those experiments which led to product formationlo are included in the Experimental Section. ~
~
The clean conversion of model substrate 7 to the glycal migration product 10, a product which has not undergone reduction, by several of the reagents studied in Table 3 led us to examine the effect of a nonreducing Lewis acid on this substrate. Treatment of glycal quinol ketal 2 with zinc chloride in ether gave 96% of the rearranged C-aryl glycal 15.
6TBS
~
(9)The reduction of indoles by diborane with a sodium methoxidel methanol quench to provide indolines is a relevant analogy to the reduction of dihydropyran 7 to tetrahydropyran 12. However, these two conversions may not be mechanistically related. See Monti, S. A.; Schmidt, R. R. Tetrahedron 1971,27,3331.
15 (96Yo)
The substitution pattern of this product is reminiscent of that in the griseusins (e.g. 3'-O-a-~-forosaminyl-(+)-
2940
Notes
J. Org. Chem., Vol. 60, No. 9, 1995
griseusin A, 16)13 and in the hybrid mederrhodin antibiotics (e.g. mederrhodin A, 17).14
16 Forosamlnyl Grlseusln A
17 MederrhodlnA
' 0
The glycal-substituted quinol ketals (e.g. 21, then, can be converted to C-aryl glycals with either of two substitution patterns (i.e. 3 by reductive aromatization or 16 by nonreductive aromatization). Thus these readily available intermediates are potential precursors to two of the four classes of naturally occurring C-aryl g1y~osides.l~ Applications of the quinol glycal chemistry to the synthesis of some of these targets is under investigation.
Experimental Section General. Flash chromatography was performed using E. Merck silica gel 60 (70-230 mesh). 4,4-Dimethoxy- l-methyl-2,5-cyclohexadien-l-ol (Sa). To a solution of 4,4-dimethoxy-2,5-cyclohexadien-l-one (Aldrich, 98%) (500 mg, 3.2 mmol) in 5 mL of THF at -78 "C was added 3.4 mL (3.22 mmol) of CH3Li (1.4 M in ether, Aldrich). The solution was stirred for 20 min at -78 "C and then quenched by the addition of 10 mL of brine. The pale yellow solution was extracted with CHzCl2 (5 x 10 mL), dried (CaS04), and concentrated to leave 494 mg (91%) of a yellow oil: 'H NMR (CDC13) 6 1.31 (s, 3H), 3.16 (bs, 1H) 3.22 ( s , 3H), 3.27 (5, 3H), 5.80 (d, J = 10.4 Hz, 2H), 6.08 (d, J = 10.4 Hz, 2H); IR (neat) 3448, 1685, 1105 cm-'; 13C NMR (CDC13) 6 138.1, 124.6, 93.1, 65.5, 49.4, 27.4; HRMS calcd for CgH1403 (M+) 170.0943, found 170.0947. 1-n-Butyl-4,4-dimethoxy.2,5-cyclohexadien-l-ol(5b). To a solution of 4,4-dimethoxy-2,5-cyclohexadien-l-one (655 mg, 4.25 mmol) in 7 mL of THF a t -78 "C was added 2.7 mL (4.32 mmol) of n-BuLi (1.6 M in hexanes, Aldrich). The resulting blue reaction mixture was stirred for 1h at -78 "C, quenched with brine (10 mL), extracted with ether (3 x 10 mL), dried (CaSOd), and evaporated to leave 879 mg (91%) of a gold-colored oil: 'H NMR (CDC13) 6 0.86 (m, 3H), 1.24 (m, 4H), 1.56 (m, 2H), 2.82 ( s , lH), 3.26 (9, 3H), 3.28 ( s , 3H), 5.89 (d, J = 10.5 Hz, 2H), 6.01 (d,J=10.5Hz,2H);13CNMR(CDC13)6137.1, 125.9,93.1,68.3, 49.5, 39.9, 25.7, 22.8, 13.8; IR (neat) 3417, 1681, 1070 cm-l; HRMS calcd for C12H2003 (M+)212.1412, found 212.1401. 4,4-Dimethoxy-l-phenyl-2,5-cyclohexadien-1-01 (5c).16 To a solution of 4,4-dimethoxy-2,5-cyclohexadien-l-one (500 mg, 3.2 mmol) in 5 mL of THF at -78 "C was added 1.68 mL (3.36 mmol) of phenyllithium (2.0 M in 70/30 cyclohexandether, Aldrich). The mixture was quenched with 10 mL of brine after 30 min, the aqueous phase was extracted with CHzClz (3 x 10 mL) and dried (CaSOd), and the solvent was evaporated to leave 691 mg (92%) of a yellow oil: IH NMR (CDC13) 6 7.60-7.15 (m, 5H), 6.12 (d, J = 10.4 Hz, 2H), 5.97 (d, J = 10.4 Hz, 2H), 3.35 (''s", 6H), 2.80 (10)The following reagents (1.3equiv) did not react with substrate 7 at 20 "C: NaBHZCN, LiBEtSH, and KB(iBu)$H. (11)A 76% yield of 5-hydroxy-l-(4-methoxyphenyl)-l-pentanone was also obtained in this reaction. (12)Friesen and Daljeett have shown that, in the hydroboratiod oxidation of C-aryl glycals, silyl migration is pH dependent and can be avoided by the use of buffer. See Friesen, R. W.; Daljeet, A. K. Tetrahedron Lett. 1990,31, 6133. (13)Maruyama, M.; Nishida, C.; Takahashi, Y.; Naganawa, H.; Hamada, M.; Takeuchi, T. J. Antibiot. 1994,47,952. (14)Omura, S.;Ikeda, H.; Malpartida, F.; Kieser, H. M.; Hopwood, D. A. Antimicrob. Agents Chemother. 1986,29,861. (15)Parker, K.A.Pure Appl. Chem. 1994,66,2135. (16)Capparelli, M. P.;De Schepper, R. E.; Swenton, J. S. J. Org. Chem. 1987,52,4953.
(s, 1H); IR (neat) 3402 cm-l; HRMS calcd for C14H1603 (M+) 232.1189, found 232.1171. 3-Bromo-4,4-dimethoxy- l-methyl-2,5-cyclohexadienl-ol (6d).17 To a solution of 3-bromo-4,4-dimethoxy-2,5-cyclohexadien-1-one (605 mg, 2.60 mmol) in 5 mL of THF at -78 "C was added 1.9 mL (2.66 mmol) of CH3Li (1.4 M in ether, Aldrich). The mixture was stirred for 90 min a t -78 "C, quenched with 5 mL of brine, and extracted with CHzCl2 (3 x 15 mL). The organic extracts were washed once each with 10 mL of saturated NaHC03, HzO, and brine and then dried over CaS04. Removal of the solvent left 637 mg (98%) of a solid, mp 89-91 "C (lit. mp 88.5-91 "C). l-Methyl-3,4,4,6-tetrametho~2,5-cyclohexadienl-ol (5e). To a solution of 3,4,4,5-tetramethoxy-2,5-cyclohexadien-l-0ne~~ (428 mg, 2.0 mmol) in 35 mL of THF at -78 "C was slowly added 2.1 mL (1.4 M, Aldrich) of CH3Li. The mixture gradually became dark orange and was stirred at -78 "C for 90 min before it was diluted with ether (100 mL) and quenched with brine (50 mL). The resulting yellow solution was extracted with ether (3 x 25 mL), dried (CaSO1), and concentrated to leave 349 mg (76%) of a yellow oil which was used immediately without further purification: lH NMR (CDC13) 6 1.47 (s, 3H), 3.15 (9, 3H), 3.23 ( s , 3H), 3.64 (s, 6H), 5.23 (s, 2H); IR (neat) 3458, 1651, 1128 em-'; HRMS calcd for CllH1805 (M+)230.1154, found 230.1169. Reductive Aromatizations of Quinol Ketals 5a-e. The procedure described for the reductive aromatization of ketal S a was applied in the reduction of ketals 5b-e. In these cases, only the following information is given: milligrams (mmol), solvent, time, and yield. All compounds exhibit physical properties consistent with the known data. 4-Methylanisole (6a).19To a solution of ketal 5a (1.4 g, 8.2 mmol) in 7.3 mL of CHzCl2 was added dropwise 1.3 equiv (1.0 mL, 10.0 mmol) of BHySMe2 (10 M in CH2C12, Aldrich) at 23 "C. After 90 min, the mixture was quenched with 1mL of brine and extracted with CHzCl2 (3 x 5 mL). The combined organic solution was washed with cold H2O (2 x 5 mL), dried (CaS04), and concentrated to give 960 mg (96%) of 6a. 4-Butylanisole (6b):20295 mg (1.39 mmol); THF (3.0 mL); 4.5 h; 187 mg (88%). 4-Phenylanisole ( 6 ~ )383 : ~ mg ~ (1.65 mmol); THF (10 mL); 4.5 h; 261 mg (86%). 2-Bromo-4-methylanisole (6d):22204 v g (0.82 mmol); CD2Cl2 (1.0 mL); 15 min; 140 mg (85%). 549 mg (2.38 mmol); CD23,4,5-"rimethoxytoluene Cl2 (2.0 mL); 6 min, 355 mg (82%). 14245,6-Dihydro-4H-pyranyl)l-4,4-dimethoxy-2,5-cyclohexadien-1-ol(7). To a solution of 5.92 mL (5.46 g, 65.0 mmol) of dihydropyran in 15 mL of THF at -78 "C was added 28.7 mL (48.8 mmol) of t-BuLi (1.7 M in pentane, Aldrich). After stirring for 10 min the solution was warmed to 0 "C and stirred for a n additional 30 min. The pale yellow lithio DHP solution was recooled to -78 "C and added via cannula to a -100 "C solution of 5.0 g (32.5 mmol) of 4,4-dimethoxy-2,5-cyclohexadien-l-one in 50 mL of ether. After 80 min the reaction was quenched by pouring into 100 mL of H2O and then extracted with ether (3 x 50 mL). The organic extracts were washed with NaHC03 (3 x 30 mL), water (2 x 20 mL), and then brine (1 x 50 mL) and dried over CaS04. Removal of the solvent left 7.64 g (99%) of a yellow oil: lH NMR (CDC13) 6 1.79 (m, 2H), 2.00 (m, 2H), 3.00 (s, lH), 3.29 ( s , 3H), 3.30 ( s , 3H), 4.02 (t, J = 5.1 Hz, 2H), 4.86 (t, J = 3.8 Hz, lH), 5.93 (d, J = 10.4 Hz, 2H), 6.18 (d, J = 10.4 Hz, 2H); IR (neat) 3396, 1666 cm-l; 13C NMR (CDC13) 6 153.5, 134.8, 126.7, 96.5,93.4, 68.0,66.6,49.9,22.0, 19.8; HRMS calcd for C13Hl804 (M+)238.1205, found 238.1222. Reaction of Ketal 7 with Borane Methyl Sulfide, Table 2. The procedure outlined for the reductive aromatization of ketal 7 (entry 3, Table 2) is applicable to the other entries. For the other entries, the only change in the procedure is the number of mole equivalents of BH3-SMe2 employed.
(17)Henton, D. R.;Anderson, K.; Manning, M. J.;Swenton, J. S. J. Org. Chem. 1980,45,3422. (18)Hart, D. J.;Cain, P. A,; Evans, D. A. J.Am. Chem. SOC.1978, 100 1.548
(19)Aldrich Chemical Co., No. 14,809-1. (20)Dewar, M. J. S.; Puttnam, N. A. J. Chem. SOC.1959,4080.
(21)Lancaster Synthesis No. 1260. (22)Trans World Chemicals, No. B2945. (23)Aldrich Chemical Co., No. 22,771-4.
J. Org. Chem., Vol. 60, No. 9,1995 2941
Notes
C-Aryl Glycal 3.6 To a solution of 5 mL (5.0 mmol) of Entry 3. To a solution of 1.50 g (6.3 mmol) of ketal 7 in 20 DIBAL-H in CHzClz (1 M, Aldrich) a t -78 "C was added mL of THF was added dropwise 0.82 mL (8.2 mmol) of BHgSMez dropwise 512 mg (1.0 mmol) of ketal 2 in 2 mL of CHzC12. After (10 M) over a 5 min period. The colorless reaction mixture was 1h a t this temperature the solution was allowed to warm slowly stirred at 23 "C for 14 h and then quenched by the addition of to room temperature over 1.5 h. The reaction mixture was 10 mL of MeOH. A 1:l solution (40 mL) of 3 N NaOH and 30% quenched by the dropwise addition of 50% methanolic CHzClz H202 was added and after effervescence was heated a t 45 "C until effervescence ceased. 2 N NaOH (2.5 mL) was added, and for 3 h. The reaction was poured into ether (3 x 50 mL), and the mixture was stirred rapidly for 30 min, filtered through the organic extracts were washed with brine (2 x 30 mL), dried Celite, extracted with brine (2 x 2 mL), and dried (NazS04). 'H (CaSOd), and chromatographed to leave 399 mg (36%) of 9,562 NMR showed a 2:l mixture of 3 and 14. This mixture was mg (47%) of 8, and 221 mg (17%) of 10. immediately dissolved in 3 mL of pyridine and treated with 0.5 4-[2.(5,sDihydro-4H-pyranyl)l~le (8): 'H NMR (CDC13) mL (822 mg, 5.3 mmol) of Poc13 for 1h a t room temperature. 6 7.36 (d, J = 6.8 Hz, 2H), 6.74 (d, J = 6.8 Hz, 2H), 5.10 (t,J = The reaction was diluted with 10 mL of EtzO and washed with 4.0 Hz, lH), 4.05 (t,J = 5.0 Hz, 2H), 3.75 (s, 3H), 2.07 (m, 2H), 1 N NaOH (2 x 1mL), HzO (2 x 2 mL), CuSO4 (2 x 2 mL), and 1.80 (m, 2H); IR (neat) 2942,2851,1651,1609,1510,1464,1344, then brine (1 x 3 mL). Drying (NazS04) and removal of the 1248,1174 cm-l; HRMS calcd for C12H1402 (M+)190.0994, found solvent left 436 mg (94%)of 3 as a colorless oil: 'H NMR (CDC13) 190.0989. 67.50(d,J=8.9Hz,2H),6.88(d,J=8.9Hz,2H),5.11(d,J= trane-3-Hydroxy-2-(4-methoxyphenyl) tetrahydropy3.2 Hz, lH), 4.30 (m, lH), 4.07 (m, lH), 3.78 ( s , 3H), 3.62 (m, ran (9): 1H NMR (CDCl3) 6 1.47 (m, lH), 1.83 (m, 2H), 2.23 (m, lH), 1.40 (d, J = 7.0 Hz), 0.9 (m, 18H), 0.15 (m, 12H); 13C NMR lH), 3.55 (m, 2H), 3.81 (s, 3H), 3.92 (d, J = 9 Hz, lH), 4.04 (m, (CDC13)G 160.0,150.9, 127.0,126.5,113.5,97.9,75.6,75.2,71.2, lH), 6.91(d,J = 8.6 Hz, 2H), 7.34 ( d , J = 8.6 Hz, 2H);I3C NMR 55.3,26.3,26.2,26.1,25.9, 17.4, -3.5, -3.6, -3.9, -4.2; IR(neat) (CDC13) 6 25.7, 31.8, 55.3, 68.3, 71.5, 85.1, 114.1, 127.8, 128.7, 1653, 1255 cm-l; HRMS calcd for C ~ 5 H 4 ~ 0 4 S (M+) i ~ 464.2778, 131.4, 159.7; IR (neat) 3397, 1613 cm-'; HRMS calcd for found 464.2740. C12H1603 (M+)208.1099, found 208.1080. C-ArylGlycoside 4b.6 To a solution of glycal 3 (172 mg, 2-[2-(5,6-Dihydro-4pyranyl)l-4-methoxyphenol(10): 'H 0.37 mmol) in 2 mL of THF was added 0.92 mL (2.5 equiv) of NMR (CDC13)6 7.63 (s, lH), 6.80 (m, lH), 6.76 (m, 2H), 5.21 (t, BHyTHF (1M in THF, Aldrich). After stirring a t 23 "C for 16 J = 4.0 Hz, lH), 4.20 (t, J = 5.0 Hz, 2H), 3.73 ( s , 3H), 2.20 (m, h, excess borane was quenched by the addition of CH30H and 1 2H), 1.85 (m, 2H); IR (neat) 3360,2949,1669,1495,1066 cm-l; mL of a 1:l mixture of 30% HzOz and 3 N NaOH was added. HRMS calcd for C12H1403 (M+) 206.0943, found 206.0951. The reaction mixture was stirred a t 23 "C for 48 h, diluted with 2-(4-Methoxyphenyl)tetrahydropyran(12): 'H NMR 10 mL of EtzO, washed with HzO (3 x 2 mL), dried (NazS041, (CDCl3) 6 7.26 (d, J = 8.6 Hz, 2 H), 6.88 (d, J = 8.7 Hz, 2 H), and concentrated to leave 91 mg (51%)of a colorless oil: 'H NMR 4.63 (t,J = 6.6 Hz, 1H), 3.80 ( s , 3 H), 3.63 (t,J = 6.4 Hz, 2 HI, (CDCl3)67.26(d,J=8.3H~,2H),6.85(d,J=8.4H~,2H),4.05 1.83 (m, 1H), 1.72 (m, 1 H), 1.58 (m, 2 H + imp), 1.41 (m, 2 HI; (d, J = 8.2 Hz, lH), 3.79 ( s , 3H), 3.50 (m, 2H), 3.41 (m, lH), 13CNMR(CDC13)622.1,32.5,38.6, 55.3,62.8,74.2, 113.9, 127.1, 3.29 (m, lH), 2.06 ( 8 , lH), 1.27 (d, J = 6.1 Hz, 3H), 0.92 ( s , 9H), 136.9,159.1; IR (neat) 3346 (imp), 2938,1612 cm-'; HRMS calcd 0.70 (9, 9H), 0.18 (s, 3H), 0.13 (s,3H), 0.05 (s, 3H), -0.63 (s, for ClzH16Oz (M+) 192.1150, found 192.1151. 1-[2-(5,f3-Dihydro-4H-pyranyl)l-4-methoxy-2,5-cyclohexa- 3H); I3C NMR (CDC13)6 159.6, 131.9, 129.3, 127.8, 113.7, 113.2, 82.4, 79.7,76.6, 76.5, 55.4,29.7,26.0, 25,9,25.8,18.7,18.2,18.0, dien-1-ol(l1).To a solution of 238 mg (1.0 mmol) of ketal 7 in -3.5, -4.2, -4.4, -5.6; IR (neat) 3405 cm-'; HRMS calcd for 1.0 mL of CHzClz a t -78 "C was added 5.0 mL (5.0 mmol) of Cz5H4605Siz (M+)482.2883, found 482.2881. DIBAL-H (1 M in CHzClZ). After 1 h, the temperature was Rearranged C-ArylGlycall5. To a solution of 54 mg (0.105 warmed to 0 "C where the solution was stirred for an additional mmol) of ketal 2 in 3 mL of ether a t -78 "C was added 0.32 mL l h and warmed to room temperature. The reaction mixture was (0.32 mmol, 3.0 equiv) of 1M ZnClz in ether. After 75 min the poured into 10 mL of 2 N NaOH and extracted with ether. solution was allowed to warm to 0 "C and then stirred for an Drying (NazS04) gave 208 mg of a 4:l mixture of 11 and 10. additional 45 min. The mixture was poured into 5 mL of Data for 11: 1H NMR (CDC13) 6 6.00 (m, 4 H), 4.82 (t, J = 3.8 saturated NaHC03, filtered through Celite and then extracted Hz, 1H), 4.32 (t,J = 1.5 Hz, 1H), 4.03 (t, J = 5.1 Hz, 2 H), 3.32 with ether. The combined extracts were washed with brine and (9, 3 H), 2.63 (9, 1 H), 2.02 (m, 2 H), 1.80 (m, 2 H); I3C NMR dried over NazSO4. Column chromatography (1:l EtOAdHex(CDC13) 6 154.6, 132.4, 127.4, 96.3, 69.5, 68.2, 66.8, 53.9, 22.2, anes) gave 48.6 mg (96%)of a yellow oil: 'H NMR (acetone-&) 19.9; IR (neat) 3397, 2928, 1665, 1065 cm-'. 6 7.93 (8, lH), 6.99 (dd, J = 1.3, 2.2 Hz, 1H), 6.78 (m, 2H), 5.61 Ketal 2.6 To a solution of 1.79 g (5.0 mmol) of L-rhamnal (d, J = 3.7 Hz, lH), 4.31 (m, lH), 4.22 (m, lH), 3.74 (m, lH), di-TBS etherZ4 in 1.6 mL of THF a t -78 "C was added 5.85 mL 3.71 (s, 3H), 1.45 (d, J = 6.7 Hz, 3H), 0.92 (''s", 18H), 0.18 ("s", (10.0 mmol) of t-BuLi (1.7 M in pentane, Aldrich). After 15 min 12H); '3C NMR (acetone-&) B 153.7, 149.9, 122.2, 118.1, 116.2, at -78 "C the solution was warmed to 0 "C. After 2 h, the 113.3, 103.6, 76.6, 75.3, 71.2, 55.9, 26.4, 26.3, 18.8, 18.6, 17.5, lithiated glycal was recooled to -78 "C and added via cannula -3.5, -3.7, -3.8, -4.1; IR (neat) 3433, 1657 cm-l; HRMS calcd to a solution of 4,4-dimethoxy-2,5-cyclohexadien-l-one (1.05 g, for C~5H~~05SizNa (M Na) 503.2625, found 503.2636. 4.5 mmol) in 7.5 mL of THF a t -99 "C over a 15 min period. The resulting blue solution was allowed to slowly warm to room Acknowledgment. We are grateful t o the National temperature over 6 h, quenched with 50 mL of brine, extracted with CHzClz (3 x 20 mL), and dried (CaS04). Column chromaInstitutes of Health ( G r a n t No. CA50720) for financial tography (50% EtOAdHex) left 1.26 g (55%) of a colorless oil: s u p p o r t of this work. 'H NMR (CDC13) 6 0.07 (m, 12H), 0.88 (m, 18H), 1.30 (d, J = 6.8 Hz, 3H), 2.72 ( s , l H ) , 3.26 (s, 3H), 3.30 (s, 3H), 3.54 (m, lH), Supplementary Material Available: Copies of IH NMR 4.02 (m, 2H), 4.86 (d, J = 3.6 Hz, lH), 5.93 (m, 2H), 6.14 (m, spectra for compounds 7-15 (9 pages). This material is 2H); I3C NMR (CDC13) 6 152.6, 134.8, 134.6, 127.6, 127.3, 98.3, contained in libraries on microfiche, immediately follows this 93.7, 76.1, 74.1, 69.2,67.9, 50.3, 50.2,25.9,25.8, 18.0, 17.9,16.7, article in the microfilm version of the journal, and can be -3.9, -4.1, -4.2, -4.4; IR (neat) 3418, 1668 cm-l; HRMS calcd ordered from the ACS; see any current masthead page for for Cz6H4&Si2 (M+) 512.2989, found 512.2957. ordering information.
+
(24) Paquette, L. A,; Oplinger, J. A. Tetrahedron 1989,45, 107.
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